疟原虫棒状体颈部蛋白2（RON2）在入侵肝细胞过程中功能研究

项目名称： 疟原虫棒状体颈部蛋白2（RON2）在入侵肝细胞过程中功能研究

项目编号： No.30872214

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 医药、卫生

项目作者： 高琪

作者单位： 江苏省血吸虫病防治研究所

项目金额： 33万元

中文摘要： 疟疾是严重危害人类健康的寄生虫病，疫苗是控制这一疾病的最佳手段，但目前尚没有有效的疫苗用于现场防治。以阻断疟原虫子孢子入侵肝细胞及其进一步发育为目标的红前期抗感染疟疾疫苗是目前较为有希望途径。但由于疟原虫子孢子入侵肝细胞的机制尚未明了，阻碍了此类疫苗的研发。本课题组前期工作发现新分离得到的疟原虫棒状体颈部蛋白 2（RON2）和裂殖子顶端膜抗原 1（AMA1）形成复合体，而且同时在疟原虫裂殖子和子孢子中表达。AMA1 被认为在入侵红细胞和肝细胞的过程中都发挥关键作用，因此 RON2 极可能不仅仅在入侵红细胞，同时在入侵肝细胞过程中也有重要功能。本项目通过对 RON2 的亚细胞定位和发生发展的研究，入侵肝细胞过程中功能的确认，以及其抗体阻断疟原虫肝细胞入侵效果的分析，来评估该蛋白作为疟疾疫苗候选分子的潜在价值，为疟疾红前期抗感染疫苗的研究提供新的途径和科学依据。

中文关键词： 疟原虫；疫苗候选分子；棒状体；肝细胞；入侵

英文摘要： Malaria is one of parasitic diseases, which is seriously hazard to human health, and anti-malaria vaccines are the best way for the disease control, but there is still no effective vaccine for field control yet. The pre-erythrocytic stage malaria vaccine is to block the Plasmodium sporozoite invasion of liver cells and their further development, became most promising approach. However, mechanisms of Plasmodium falciparum sporozoite invasion of liver cells are not still clear yet, which hindering the development of such vaccines. Our group previously revealed a novel Plasmodium rhoptry neck protein 2 (RON2), which formed a complex with merozoite apical membrane antigen 1 (AMA1), and had expression in both Plasmodium falciparum merozoite and sporozoite. AMA1 is considered to play a key role in the process of the invasion of red blood cells and liver cells, so RON2 has most likely important functions not only in the invasion of red blood cells, but also in the process of invasion of liver cells. Here, we studied the subcellular localization and development process of RON2, and investigate its functions in the process of the invasion of liver cells, and analysis the effect of its antibody blocking malaria parasite invasion of liver cells to assess the potential value of the protein molecule as a malaria vaccine candidate molecule. The study provided new target and scientific basis for pre- erythrocytic stage malaria vaccine research.

英文关键词： Plasmodium; Vaccine Candidate; Rhoptry; Hepatocyte; Invasion